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CN101835449A - 4-amidino benzylamines for cosmetic and/or dermatological use - Google Patents

4-amidino benzylamines for cosmetic and/or dermatological use Download PDF

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Publication number
CN101835449A
CN101835449A CN200780100405A CN200780100405A CN101835449A CN 101835449 A CN101835449 A CN 101835449A CN 200780100405 A CN200780100405 A CN 200780100405A CN 200780100405 A CN200780100405 A CN 200780100405A CN 101835449 A CN101835449 A CN 101835449A
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acid
skin
alkyl
lys
benzyl
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R·沃格里
H·齐格勒
M·吉姆佩勒
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DSM IP Assets BV
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0208—Tissues; Wipes; Patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0212—Face masks
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216—Solid or semisolid forms
    • A61K8/0229—Sticks
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/042—Gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/046—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/007—Preparations for dry skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/87—Application Devices; Containers; Packaging
    • A61K2800/872—Pencils; Crayons; Felt-tip pens

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
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  • Dermatology (AREA)
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  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

This invention relates to the use of 4-amidino benzylamine derivatives as cosmetic ingredients and to cosmetic compositions, as well as to non-therapeutic methods for the cosmetic treatment of the skin and the scalp. Said derivatives and compositions can be used as urokinase inhibitors to prevent and restore damage of the epidermal barrier. Barrier abnormalities and disruptions respectively are often the starting point of a dry skin state, of itching, of dandruff and of the perception of sensitive skin. These 4-amidino benzylamine derivatives can be used for topical skin and scalp care applications in form of creams, lotions, gels, shampoos and the like.

Description

The 4-amidino benzylamines is used to improve looks and/or the purposes of dermatological
Background technology
Urokinase (uPA) also is urokinase-type plasminogen activator, is a kind of Multidomain serine protease (EC 3.4.21.31).UPA is a kind of 411 amino acid residue albumen, comprises three domains: class somatomedin domain (aa 4-43), kringle domain (aa 47-135) and catalysis " B " chain (amino acid/11 44-411).This kringle domain shows as heparin-binding.Therefore such somatomedin domain has the structure that some are similar to epidermal growth factor (EGF), and is used as a kind of EGF domain and is mentioned.UPA is synthesized and is proenzyme (pro-uPA or strand uPA), and by being activated by the fibrinolysin Proteolytic enzyme cracking between Lys158 and the Ile159.Two kinds of product chains keep together by disulphide bond 1
For example smooth muscle cell, fibroblast, endotheliocyte, macrophage and tumor cell produce uPA by a large amount of cell types.It involves in the cell invasion and tissue remodeling on as pivotal player 2
In extracellular matrix, uPA is incorporated into cell membrane by the reciprocal action of itself and special cells surface receptor uPA receptor (uPAR).Describedly obviously regulate by class EGF domain in conjunction with reciprocal action.When Pro-uPA and plasminogen during by receptors bind, pro-uPA is accelerated to the cracking of active uPA.Therefore, the serine protease fibrinolysin activates pro-uPA, and it is successively by the more fibrinolysins of the original activation of division fibrinolysin.This positive feedback loop obviously is limited to the proteolysis based on receptor at cell surface, because find to have excessive greatly protease inhibitor in blood plasma 1
The endogenous of most important uPA (endogeneous) inhibitor is the plasminogen activator inhibitor-1 (PAI-1) and the plasminogen activator inhibitor-2 (PAI-2) of serpin, its irreversible Profilin enzymatic activity.
The primary substrate of uPA is a plasminogen, and plasminogen is converted into fibrinolysin by cell surface in conjunction with uPA.UPA is high special for single peptide bond in plasminogen.Activatory fibrinolysin degradation of cell epimatrix composition (fibrin, fibronectin, laminin and Dan Baijutang) and activation matrix metalloproteinase (MMPs), thereby the decomposition of promotion collagen 1,3,4The important process of this activity guiding, described process relates to cell invades and tissue remodeling, and comprises that repair in trauma, bone reproduce, blood vessel takes place, tumor is invaded and the metastasis diffusion 2
Many cell types use uPA as for example crucial initiation factor of extracellular matrix (ECM) and basement membrane (BM) modification of the proteolytic degradation of fibrinolysin mediation or extracellular supporting construction.Existence in the material framework that cell is provided by ECM and BM in tissue and organ, mobile and interact with each other.Cell is in ECM or pass the local proteolysis decomposition of mobile needs of BM or the modification of these structures, invades adjacent domain to allow cell, and described adjacent domain was inaccessible for cell in the past 5
Therefore the uPA inhibitor has the activity of angiogenesis inhibitor, arthritis, inflammation, intrusion, transfer, osteoporosis and inhibition tumor growth 3
Owing to the huge range of the intrusion biological process that mediates with uPA, effectiveness effective and optionally uPA inhibitor is highlighted 2
Owing to have the enormous quantity of the specific serine protease of trypsinlike enzyme, comprise factor VII, factor X and types of organization's activator of plasminogen (tPA), uPA exploitation effective and selective depressant is a challenge.Provide effectively based on the drug development of structure widely and uPA inhibitor optionally.They generally are the arginine analogies (arginino mimetics) with amidine or guanidine functional group 6, described functional group is constructed on aromatic series or the heterocycle support.
In the past few decades, beauty treatment industry is at different body parts, with variation in the horizontal endocuticle structure in different horny layer (SC) space, component and function increasing concern arranged in the Various Seasonal in every year.For example, appear at different body parts in that the difference of horny layer lipid or NMF (nature moisturizing factor) level is known, reduction level in the winter months in every year, and reduce towards its level of cuticular outside.
The difference of proteinase activity and contents level is also reported.Shown that epidermis expresses several multiple active serine proteases that relate in skin, the multiple activity that relates in the described skin is: the dynamic equilibrium of the propagation of epidermis, differentiation, lipid barrier and the remould of tissue.Most important, be definite event before the decortication by the proteolysis of serine protease and other enzymes horny layer corneodesmosome together 7Because lipid is handled the degraded of enzyme and unwind (corneodesmolysis) in the flat uncontrolled lasting keratinization of high pH value water, the extreme of serine protease is active to cause the barrier disturbance, thereby horny layer integrity and cohesiveness are worsened 8
Serine protease in horny layer can be the key point to potential and non-visible sometimes dermatitis disease.In this respect, the activity of the plasminogen of raising/fibrinolysin system is considered to damage barrier and recovers, and assists barrier to recover as protease inhibitor 9Reported that uPA is activated in the following barrier infringement 10The uPA activity that increases is observed from the tape stripping experiment (tapestrippings) from the buccal of the experimenter with dry skin, and described dry skin is relevant with the transepidermal water loss level of increase 11Protease inhibitor particularly trypsin-type inhibitor is reduced dry skin by report 9,10,11
People such as Kitamura 12Further prove plasminogen, it only is positioned at normal subjects's basal layer, expresses in whole cuticular celluloses of dry skin.Yet, people such as Kawai 11Report uPA is present in horny layer and this kind of enzyme is the activated trigger of the plasminogen system inside horny layer.UPA is raised in the experimental inductive dry skin on the skin of back of individuality.They further prove, the uPA activity of increase is present in from the experimenter of obvious dry skin and has in experimenter's the horny layer sample of buccal of TEWL level of raising.If the experimenter has the skin of normal appearance and is lower than about 16g m -2h -1TEWL, so find active.These conclusions show barrier form not normal and or barrier to recover impaired generation be because TEWL and the plasmin activity that improves, and the approach of barrier reparation will be to use protease inhibitor.Although in fact the experimenter has and seems normal skin clinically; Described may be owing to induce on the face under the environmental effect and cause subclinical little inflammatory symptoms in the level that improves on the face.
Multiple barrier destruction can cause the hyperplasia of epidermis and be considered to cause dry skin 10
Astonishing discovery is at WO01/96286 4In the uPA-inhibitor described can be used for Local treatment skin and the scalp barrier is unusual, as the dry skin situation, itch, the dandruff and sensitive-skinned consciousness.
Summary of the invention
The present invention relates to 4-amidino benzylamines derivant prepares the non-therapeutic purposes of beauty treatment and dermatological compositions and beautifying skin treatment as beauty treatment composition and being used for the purposes of method.Described 4-amidino benzylamines derivant has following general formula (I)
Wherein
R 1Expression H, C 1-C 8-alkyl, the optional aryl-C that replaces 1-C 4-alkyl, amino-C 1-C 5-alkyl or hydroxyl-C 1-C 5-alkyl;
R 2Expression H or C 1-C 8-alkyl;
R 3Expression hydroxyl-C 1-C 5-alkyl or C 1-C 8-alkyl;
R 4Expression H ,-SO 2-R ,-CO-R or-COO-R;
R 5The expression H, OH ,-CO-R or-COO-R;
R represents C 1-C 16-alkyl, the optional aryl that replaces, the optional heteroaryl that replaces, the optional aryl-C that replaces 1-C 4-alkyl or the optional heteroaryl-C that replaces 1-C 4-alkyl and
X represents CH or N.
The preferred compound of general formula (I), wherein amidino groups functional group is positioned at No. 4 positions of phenyl ring and/or wherein
R 1Expression H, C 1-C 8-alkyl, the optional aryl-C that replaces 1-C 4-alkyl or amino-C 1-C 5-alkyl;
R 2Expression H;
R 3Expression hydroxyl-C 1-C 5-alkyl;
R 4Expression-SO 2-R;
R 5Expression H;
R represents the optional aryl-C that replaces 1-C 4-alkyl and
X represents CH.
Preferred amidino benzylamines derivant is benzyl sulfonyl-D-Ser-homoPhe-(4-amidino groups-benzyl amide (benzylamide)), benzyl sulfonyl-D-Ser-Lys-(4-amidino groups-benzyl amide), benzyl sulfonyl-D-Ser-Gly-4-amidino groups-benzyl amide and benzyl sulfonyl-D-Ser-Ala-4-amidino groups-benzyl amide.All these compound exhibits effectively and high special urokinase-inhibitions activity and being described among the WO01/9626864.The pure enantiomer of use that these chemical compounds are suitable.
Term " heteroaryl " for it is own independent or as a kind of structural element that comprises the group of heteroaryl, refers to the first aroma system of the 5-11 that is made up of one or two ring, and wherein 1 to 3 yuan is hetero atom, is selected from oxygen, sulfur and nitrogen.1 to 2 phenyl ring can be condensed into heterocycle.It is pyridine radicals, pyrimidine radicals, pyridazinyl, pyrazinyl, 1 for example, 3,5,-triazine radical, quinolyl, isoquinolyl, quinoxalinyl, quinazolyl, phthalazinyl, pyrrole radicals, pyrazolinyl, imidazolinyl, 1,2,4-triazolyl, tetrazole base, furyl, thienyl, oxazolinyl, thiazolinyl, isothiazoline base, benzoxazolyl, Thianaphthene base, indyl, benzimidazolyl, indazolyl, benzotriazole base and benzothiazolyl.Connection can at random occur in heterocyclic moiety or in benzo part with on nitrogen-atoms or arbitrarily in the π-mistake hetero atom on the carbon atom.
The substituent group of optional aryl that replaces and heteroaryl is halogen, C for example 1-C 6-alkyl, C 1-C 6-haloalkyl, hydroxyl, C 1-C 6-alkoxyl, C 1-C 6-halogenated alkoxy, C 1-C 6-thiazolinyl, C 2-C 6-alkene oxygen base, C 2-C 6-alkynyl, C 3-C 6-alkynyloxy group, C 1-C 6-alkoxy carbonyl group, CN, OCN, nitro, amino, C 1-C 6-alkyl amino, two-C 1-C 6-alkyl amino, amino carbonyl, C 1-C 6-alkyl amino-carbonyl, two-C 1-C 6Alkyl amino-carbonyl, C 1-C 6-alkylthio, C 1-C 6-alkyl sulfo group (alkylsulfoxyl), C 1-C 6-alkyl sulphonyl and C 3-C 6-cycloalkyl.
These chemical compounds can be used in the cosmetic applications, use with forms such as cream frost, emulsion, gel, shampoos, and it is unusual to be used to handle skin and/or scalp barrier, as dry skin symptom, pruritus, the dandruff and/or sensitive-skinned consciousness.
According to the effective benzyl amine derivative in part of the present invention can usefully make ground or be prepared into any serious hope and want the administration form that obtains.Therefore, these preparations can be for example moisture or the Emulsion of anhydrous formulation, Water-In-Oil (w/o) or oil-in-water (o/w) form or microemulsion, multiple Emulsion, for example W/O/W (w/o/w) type, gel, shampoo, solid or aerosol.Preparation of the present invention can be used with the form of for example powder, wet patch (wet patch), lotion, cream frost or ointment, shampoo or lotion preparation or other beauty treatment approvals.The valid density of benzyl amine derivative is about 0.001-10000ppm based on the gross weight of cosmetics, preferred 0.1-1000ppm.
The present invention's effective benzyl amine derivative of improving looks, it also can be introduced into preparation or goods, can with arbitrarily other, use usually and local application skins based upon bidding nursing composition uses.The example of additional skin nursing composition comes from plant, algae, microalgae, yeast, mushroom, animal and microorganism, synthetic and semi-synthetic material.
Melatonin, carbamide, kreatinin, dimethylethanolamine and derivant thereof,
Aminoacid and derivant thereof (for example serine, glycine, asparagine, cysteine, glutamine, lysine, arginine, aspartic acid, glutamic acid, N-acetylcystein, citrulline),
Protein, their hydrolyzate and derivant thereof (for example collagen protein, colloid, albumin, casein, elastin laminin, keratin, sericin, fibroin, anti-keratin microfilament are assembled albumen (fillagrin)),
Somatomedin and derivant thereof (for example transforming growth factor, insulin like growth factor, epidermal growth factor, acidity and alkaline fiber archeocyte somatomedin, nerve growth factor, keratin somatomedin, hepatocyte growth factor, platelet-derived somatomedin, granulocyte macrophage colony stimulating factor, vascular endothelial cell growth factor)
Enzyme and protease and derivant thereof (papain, bromelain, subtilisin, peroxide dismutase, phospholipase, T-5398),
Enzyme inhibitor, protease inhibitor and derivant thereof (for example tranexamic acid, soybean trypsin inhibitor, Bao Man-Bi Erke (Bowman Birk) inhibitor, LEKTI, aprotinin, elastin, SLPI, alpha1-antitrypsin, α 1-chymotrypsin inhibitor, cholesterol sulfate, leupeptin, chymostatin, tissue inhibitor of metalloproteinase, Series compound, mustard extract),
Coenzyme and derivant thereof (for example coenzyme Q10 (ubiquinon), nicotiamide, nicotinamide adenine dinucleotide, nicotinamide-adenine dinucleotide phosphate, coenzyme A, actimide, flavin adenine dinucleotide, flavin mononucleotide (FMN)),
Peptide for example two-; three-; four-; five-and six peptides and derivant thereof (carnosine for example; H-β Ala-Pro-Dab-NH benzyl; Cu (II)-H-Gly-His-Lys-OH; H-Gly-Leu-Phe-OH; (anti--9) vaccenic acid (Elaidyl)-Lys-Phe-Lys-OH; palmityl-Lys-Val-Lys-OH; H-Lys-Pro-Val-OH; palmityl-Lys-Val-Dab-OH; H-Arg-Ser-Arg-Lys-OH; palmityl-Lys-Val-Dab-Thr-OH; H-Gly-Pro-Arg-Pro-Ala-NH2; palmityl-Lys-Thr-Thr-Lys-Ser-OH; acetyl group-Glu-Glu-Met-Gln-Arg-ArgNH2)
Carbohydrate is for example single-, two-, three and oligosaccharide class and derivant (for example glucose, fructose, mannose, dihydroxy acetone, Erythrulose, sucrose, trehalose, maltose) thereof,
Polysaccharide and derivant thereof (for example galactomannan, glucomannan, beta glucan, carrageenan, glycogen, chitosan, lentinan, lichenin, inulin, fucose, alginate, xyloglucan, glucosan, amylose, levan, xanthan gum, amylopectin)
The glycosaminoglycan class, their subunit (subunits) and derivant thereof (for example hyaluronan, chondroitin sulfate, heparin, dermatan sulfate, glucuronic acid, N-acetyl-glucosamine),
Purine, pyrimidine, nucleotide, nucleoside and derivant thereof (for example allantoin, uric acid, adenosine, adenosine monophosphate, adenosine 5 '-triphosphoric acid, kinetins),
Carboxylic acid and derivant thereof (for example lactic acid, citric acid, glycolic, Azelaic Acid, salicylic acid, thioctic acid ketopyrrolidine (pyrrolidon) carboxylic acid, urocanic acid, caffeic acid),
Fatty acid and derivant thereof (for example linoleic acid, oleic acid, Palmic acid, conjugated linoleic acid),
Lipid and derivant thereof (for example squalane, Squalene, monoglyceride, diglyceride, triglyceride, vaseline, lanoline),
Sphingol, sphingolipid, glycosyl sphingolipid, thioester and derivant thereof (for example phytosphingosine, ceramide, glycoeeramide, cerebroside, ganglioside (gangliobrosides), sulfatide),
Phospholipid and derivant thereof (phosphatidylcholine, Phosphatidylserine, phosphatidyl ethanolamine),
Sterol, plant sterol, saponin and derivant thereof (for example cholesterol, sitosterol, stigmasterol, brassicasterol (kampesterol), lupeol, glycyrrhizin),
Flavonoid and derivant thereof (for example rutin, Quercetin, genistein, daidzein, fisetin, myricetin, luteolin, hesperetin, silibinin, silymarin, apigenin),
Phenol, polyphenol and derivant thereof (for example epigallocatechin, epigallocatechin gallate, resveratrol, nordihydroguaiaretic acid, ellagic acid, resorcinol),
Terpene and derivant thereof (for example enoxolone, farnesol, α-bisabolol, β-bisabolol),
Alkaloid and derivant thereof (for example caffeine, theophylline, theobromine),
Benzofuran and derivant thereof (for example lichenic acid),
Trace element (for example Zn, Se, Mn) and salt thereof,
Polyhydric alcohol and derivant thereof (for example glycerol, propylene glycol, butanediol, sorbitol, erithritol, hexanediol, plant triol (phytantriol)),
Antimicrobial composition, antimicrobial peptide and derivant thereof (for example pyrrole sulfur zinc, sozin, cathepsin inhibin, skin enemy rhzomorph, histatins (histatin)),
UV absorbent and derivant thereof (benzoate, anthranilate, Salicylate, cinnamate, benzophenone (Parsol for example for example TM340), benzimidazole, benzotriazole (Tinosorb for example TMM), triazine (Tinosorb for example TMS), polysiloxanes (Parsol for example TMSLX), titanium oxide, zinc oxide, melanin, avobenzone),
Vitamin, provitamin and derivant thereof (for example vitamin A, the vitamin of B series, vitamin C, vitamin D, vitamin E),
Retinoid and derivant thereof (for example retinal, retinal, tretinoin, isotretinoin, alitretinoin, etretinate, acitretin, tazarotene, bexarotene),
Carotenoid and derivant thereof (for example alpha-carotene, beta-carotene, lycopene, luteine (luteine), cryptoxanthin, astaxanthin),
Chelating agen and derivant thereof (for example ethylenediaminetetraacetic acid, deferoxamine,, furil-dioxime (furildioxime)),
Wetting agent (for example glycerol, butanediol, sorbitol, carbamide, N-acetyl-glucosamine, hyaluronic acid, glycosaminoglycan, aminoacid,, protein hydrolysate, collagen, list, two-, few-and polysaccharide,
Figure BPA00001178290700071
),
Regulate epidermal barrier function agent (for example ceramide, cholesterol, fatty acid, squalane, phytosphingosine, lanoline, lecithin, vaseline),
Skin recovers and (for example regenerates composition
Figure BPA00001178290700072
Yeast extract, comfrey extract (symphytum extract), Semen Ginkgo extrac),
Skin-tightening and anti-wrinkle agent (for example Herba Centellae,
Figure BPA00001178290700081
Biopeptide CL, Kollaren PP, (anti--9) vaccenic acid-Lys-Phe-Lys-OH, H-Arg-Ser-Arg-Lys-OH, Argireline, Collaxyl, Dermican LS 9745),
Alleviate (soothing) and antiinflammatory (for example Flos Chrysanthemi extract (chamomile extract), pantothenylol, nicotiamide, zinc oxide, aloe vera (aloe vera), Flos Inulae extract, Radix Glycyrrhizae extract, Radix Hamamelidis Mollis extract, Sensicalmine, Alistine, H-Lys-Pro-Val-OH)
The antipruritic composition (for example
Figure BPA00001178290700083
Radix Oenotherae erythrosepalae oil),
Anti-dandruff composition (for example allantoin, selenium sulfide, bifonazole, pyrrole sulfur zinc),
Decortication composition (for example alpha-hydroxy acid, beta hydroxy acid),
Antioxidant (for example superoxide dismutase, ubiquinone, thioctic acid, vitamin E, green tea extract),
Sebum adjusting and anti-acne agent are (for example
Figure BPA00001178290700084
Linoleic acid, prunus africana extract, Flos Carthami Thymi Serpylli Herba extract (thymus officinalis extract), resorcinol, salicylic acid),
Regulate tractive vestige reagent (for example Herba Centellae extract, Darutosid, Registril),
The skin immune system regulator (for example the arnica montana extract, ),
Skin lightener (for example alpha-arbutin, β-arbutin, kojic acid, ascorbyl magnesium phosphate, Radix Glycyrrhizae extract, Melanostatin (Melanostatine), acetyl group-Asn-Ser-Leu-Asp-Phe-NH 2),
Skin tanning agent (skin tanning agents) (Erythrulose, dihydroxy acetone (dihydroxyacteone), Melitane PP),
Anti--fat agent (for example caffeine, theophylline, Guarana extract,
Figure BPA00001178290700087
),
Regulate skin microcirculation reagent (for example arginine, silibinin, silymarin),
Regulate for example reagent (for example metronidazole, Azelaic Acid) of flushing and astable erythema (nontransient erythema) of rosacea principal character,
Regulate little blood streak (couperose) and telangiectasis agent (for example silymarin),
Anti-fungal composition (for example ketoconazole (ketokonazole), ciclopirox olamine (cyclopyrox), tea tree oil),
And composition thereof.
Acceptable carrier can be used for preparing cosmetic activity compositions of the present invention or preparation usually.The example of carrier is alcohol, polyhydric alcohol, fatty acid, lipid, oil, wax, thickening agent, surfactant, emulsifying agent, filler, antiseptic, essence and fragrance and stain, foam stabiliser and/or silicone like this.
Be used for carrier of the present invention particularly glycerol, bound to polyglycerol compound, ethylene glycol, propylene glycol, Polyethylene Glycol, polypropylene glycol, ethanol, isopropyl alcohol, agar, gum tragacanth, Radix Acaciae senegalis, plant and animal gelatin, methylcellulose, ethyl cellulose, carboxymethyl cellulose, methylol fiber, hydroxypropyl cellulose, sodium alginate, polyvinyl alcohol, polyvinyl alcohol acetate, C 6-22Aliphatic alcohol is spermol, C for example 6-22Aliphatic alcohol ester, particularly stearic acid, Palmic acid, lauric acid and corresponding methyl, ethyl and propyl diester, lanoline, aqueous paraffin wax or natural or synthetic wax, for example vaseline or Cera Flava, vegetable oil for example olive oil, Oleum Cocois, soybean oil, Oleum Ricini and corresponding hydrogenated oil and fat, with the hydroxy-containing compounds of poly-alkyl oxygen modification, and more become known for raw material in the cosmetic formulation.
In order to prepare Water-In-Oil (w/o), oil-in-water (o/w) or W/O/W (w/o/w) Emulsion or microemulsion, preferred use itself is known and be used for this purpose chemical compound.In order to prepare the fat phase, mineral and natural oil or wax are preferred.With the synthetic ester that obtains of producing of pure and mild fatty acid, for example fatty acid ester of ethanol, propanol, isopropyl alcohol, propylene glycol or glycerol or organically C 3-20The aliphatic alcohol ester of fatty acid also is available.For example myristic acid, Palmic acid, stearic acid, oleic ester, for example propyl myristate, isopropyl palmitate, isopropyl stearate, acid isopropyl, butyl stearate, lauric acid hexyl ester, stearic acid 2-hexyl decyl ester, perhaps natural oil, for example Simmondsia chinensis oil or its mixture are preferred.Preferred silicone is dimethyl polysiloxane particularly, preferred ring-type or linear form.
And preparation of the present invention can comprise and be used for acid or the alkali that pH value is regulated, for example sodium hydroxide, phosphoric acid, and citric acid or lactic acid, triethanolamine are preferably as buffer system.
The scope that following embodiment attempts to explain the present invention more specifically rather than limits it in any form.
Embodiment
Embodiment 1
The preparation of Emulsion
The A phase constituent is heated to 70 ℃ and B phase constituent and is heated to 75 ℃.Under agitation B is slowly joined the A phase mutually.Mixture is cooled to 50 ℃, homogenizing and be cooled to 30 ℃.Add C phase and D phase constituent then.Stir Emulsion until arriving room temperature.
Phase Composition ??％m/m
??A Polyglycereol-3-methyl glucose distearate (Tego Care 450) ??3.00
16/octadecanol ??2.25
Tristerin ??2.25
??Cetiol?868 ??10.00
Squalane ??5.00
??B Water ??66.99
Hyaluronate sodium ??5.00
??C Glycerol ??5.00
Phase Composition ??％m/m
??Phenonip ??0.50
??D Benzyl sulfonyl-D-Ser-Gly-(4-amidino groups-benzyl amide) ??0.01
Embodiment 2
The preparation of beauty-care gel
The A phase constituent under agitation dissolves.Regulate pH value to 6.0 mutually and add the C phase then with B.
Phase Composition ??％m/m
??A Water ??92.09
1,3 butylene glycol ??5.00
??Phenonip ??0.50
??AbilB?8843 ??1.50
Carboxymethyl cellulose ??0.15
Carbopol Ultrez 10 ??0.75
??B ??NaOH
??C Benzyl sulfonyl-D-Ser-Gly-(4-amidino groups-benzyl amide) ??0.01
Embodiment 3
The active mutual relation of TEWL and fibrinolysin and uPA in the horny layer
The Caucasia experimenter of ten health (skin type II-III) adds this research.All volunteers have signed Informed Consent Form.Buccal carry out the experiment of successive tape stripping (
Figure BPA00001178290700101
CuDermCorporation, Dallas, (9 times) USA) before, (Biox Systems, London UK) measure TEWL to use Aquaflux AF103.The experimenter was required before horny layer is sampled not use at least 12 hours any topical drug or cosmetics.At first, before the tape stripping step 15 minutes, skin was with the careful cleaning of the wetted cotton pad of distilled water under the ambient temperature and allow dry.Make the environment space endoadaptation of experimenter under standard conditions.Skin site is with surgery label labelling, to guarantee measuring probe and the adhesive tape beginning
Be administered to identical zone eventually.
Standard
Figure BPA00001178290700102
Dish has diameter and the 3.8cm of 2.2cm 2Area, (CuDerm Corporation, Dallas is USA) at 225g/cm with pressure apparatus 2Be placed into skin last 5 second under the pressure.Peeling off gap periods is 20 ± 5 seconds.
The protein content of tape stripping is by using infrared light densimeter SquameScan TM850A (Heiland electronic, Wetzlar, Germany) quantitative at 850nm place absorptiometry.SquameScan TM850A is in particular standard
Figure BPA00001178290700103
The Application Design of dish.Concerning quantification of protein, use following equation:
C Albumen[μ g cm -2]=1.366* absorbs [%]-1.557
Each tape stripping is transferred to 1.5ml microcentrifugal tube (Eppendorftube) immediately after absorptiometry, is to extract 15 minutes with 25 ℃ and 1000rpm in 8.0 the buffer agent at the pH value that the 0.1M Tris/HCl of 750 μ l and 0.5%Triton X-100 form then.The extract of tape stripping is mixed.1.25 μ l is dissolved in 5mM fluorescent probe urokinase substrate B z-β-Ala-Gly-Arg-AMC (Pentapharm among the DMSO, Switzerland) and fibrinolysin substrate MeOSuc-Ala-Phe-Lys-AMC (Bachem Switzerland) is added in the solution (final substrate concentration=25 μ M) of 250 μ l.This solution mixes under 37 ℃ and 1000rpm.This acetic acid of 1% that is reflected at after 2 hours by adding 100 μ l is stopped in the reactant mixture of 100 μ l.The AMC that discharges by C18 HPLC linear gradient elution method by quantitative (80% water/20% acetonitrile/0.07%TFA to 50% water/50% acetonitrile/0.07%TFA).The post that uses is Symmetry C18,3.5 μ M, 4.6mmx75mm (Waters, Milford, USA).Flow velocity is 1ml/min, and volume injected is that the retention time of 5 μ l and AMC is 3.5 minutes.Emission wavelength is that 442nm and excitation wavelength are 354nm.
Data are summarised among table 1 and Fig. 1.This conclusion has been supported in the existence of uPA and plasmin activity in the cuticular top layer of the mankind, and these protease can suppress by the inhibitor of local application.
The TEWL of 9 cellular layers in top and the mensuration of uPA and fibrinolysin level in table 1:10 name experimenter's the horny layer.
The experimenter ??TEWL??[gm -2h -1] ??uPA??[nUμg -1Protein] Fibrinolysin [nU μ g -1Protein]
??01 ??41.7 ??2.89 ??5.59
??02 ??31.2 ??1.81 ??3.59
??03 ??26.2 ??1.80 ??2.54
??04 ??33.0 ??2.04 ??4.47
??05 ??16.1 ??1.43 ??1.52
??06 ??23.8 ??0.94 ??2.85
??07 ??21.0 ??2.02 ??1.84
??08 ??20.8 ??1.23 ??1.88
The experimenter ??TEWL??[gm -2h -1] ??uPA??[nUμg -1Protein] Fibrinolysin [nU μ g -1Protein]
??09 ??22.3 ??1.47 ??2.41
??10 ??25.6 ??2.46 ??3.13
List of references
1.Rosenberg.，S.；Doyle，，M.V.Peptide?inhibitors?of?urokinase?receptoractivity。US5656726，1997。
2.Barber；C.G.；Dickinson，R.P.2-Pyridinylguanidine?urokinase?inhibitors。EP1044967，2000-10-18，2000。
3.Sasaki，T.；Nojima?，M.Ozonide?compounds?with?inhibitory?activity?forurokinase?production?and?angiogenesis。US6365610，2002。
4.Stürzebecher，J.；Steinmetzer，T.；Künzel，S.；Schweinitz，A，UrokinaseInhibitors。WO?01/96286，20.12.2001，2001。
5.Bridges，A.；Schwartz，C.E.；Lottlefield，B.A.Benzothiophenes?andthienothiophenes?and?related?compounds?useful，for?example，as?urokinaseinhibitors。EP0568289，1993-11-03，1993。
6.Deck，L.M.；Vander?Jagt，D.L.；Heynekamp，J.J.Isocoumarin-basedinhibitors?of?urokinase-type?plasminogen?activator。US2006252823，2006-11-09，2006。
7.Rawlings，A.V.；Matts，P.J.，Stratum?Corneum?Moisturization?at?theMolecular?Level：An?Update?in?Relation?to?the?Dry?Skin?Cycle。J?Invest?Dermatol2005，124。(6)，1099-1110。
8.Hachem，J.-P.；Man，M.-Q.；Crumrine?，D.；Uchida，Y.；Brown?，B.E.；Rogiers，V.；Roseeuw，D.；Feingold，K.R.；Elias，P.M.，Sustained?SerineProteases?Activity?by?Prolonged?Increase?in?pH?Leads?to?Degradation?of?LipidProcessing?Enzymes?and?Profound?Alterations?of?Barrier?Function?and?StratumCorneum?Integrity。J?Invest?Dermatol?2005，125，(3)，510-520。
9.Denda，M.；Kitamura，K.；Elias，P.M.；Feingold，K.K.，trans-4-(Aminomethyl)cyclohexane?Carboxylic?Acid(T-AMCHA)，an?Anti-FibrinolyticAgent，Accelerates?Barrier?Recovery?and?Prevents?the?Epidermal?HyperplasiaInduced?by?Epidermal?Injury?in?Hairless?Mice?and?Humans。J?Invest?Dermatol1997，109，(1)，84。
10.Katsuta，Y.；Yoshida，Y.；Kawai，E.；Kohno，Y.；Kitamura，K.，Urokinase-type?plasminogen?activator?is?activated?in?stratum?corneum?afterbarrier?disruption。J?Dermatol?Sci?2003，32，(1)，55-57。
11.Kawai，E.；Kohno，Y.；Ogawa，K.；Sakuma，K.；Yoshikawa，N.；Aso，D.，Can?Inorganic?Powders?Provide?Any?Biological?Benefit?in?StratumCorneum，While?Residing?on?Skin?Surface。IFSCC?Magazine?2002，5，(4)，269-275。
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Claims (17)

1. at least a chemical compound of following general formula (I) as the beauty treatment composition purposes,
Figure FPA00001178290600011
Wherein
R 1Expression H, C 1-C 8-alkyl, the optional aryl-C that replaces 1-C 4-alkyl, amino-C 1-C 5-alkyl or hydroxyl-C 1-C 5-alkyl;
R 2Expression H or C 1-C 8-alkyl;
R 3Expression hydroxyl-C 1-C 5-alkyl or C 1-C 8-alkyl;
R 4Expression H ,-SO 2-R ,-CO-R or-COO-R;
R 5The expression H, OH ,-CO-R or-COO-R;
R represents C 1-C 16-alkyl, the optional aryl that replaces, the optional heteroaryl that replaces, the optional aryl-C that replaces 1-C 4-alkyl or the optional heteroaryl-C that replaces 1-C 4-alkyl and
X represents CH or N.
2. according to the purposes of the described at least a chemical compound of claim 1, it is characterized in that phenyl ring is to be replaced by amidino groups functional group No. 4 positions.
3. according to the purposes of one of claim 1 and 2 described at least a chemical compound, it is characterized in that R 1Expression H, C 1-C 8-alkyl, the optional aryl-C that replaces 1-C 4-alkyl or amino-C 1-C 5-alkyl;
R 2Expression H;
R 3Expression hydroxyl-C 1-C 5-alkyl;
R 4Expression-SO 2-R;
R 5Expression H;
R represents the optional aryl-C that replaces 1-C 4-alkyl and
X represents CH.
4. at least a purposes in the chemical compound according to claim 1, described chemical compound is as follows:
A) benzyl sulfonyl-D-Ser-Gly (4-amidino groups-benzyl amide)
B) benzyl sulfonyl-D-Ser-Ala-(4-amidino groups-benzyl amide)
C) benzyl sulfonyl-D-Ser-homoPhe-(4-amidino groups-benzyl amide)
D) benzyl sulfonyl-D-Ser-Lys-(4-amidino groups-benzyl amide).
5. according to the purposes of one of claim 1-4 described at least a chemical compound, it is characterized in that chemical compound exists with the form of the salt of suitable dermatological.
6. according to the purposes of one of claim 1-5 described at least a chemical compound, it is characterized in that chemical compound exists with pure enantiomer.
7. be used to prepare the purposes of cosmetic composition according to the described at least a chemical compound of one of claim 1-6.
8. according to the purposes of claim 7, it is characterized in that described compositions is from 0.001 to 10000ppm (m/m), preferably contains formula (I) chemical compound from 0.1 to 1000ppm (m/m) with concentration range.
9. a cosmetic composition, particularly local application cosmetic composition is characterized in that containing
A) at least a chemical compound of general formula (I) and
B) at least a additional skin nursing composition is selected from aminoacid, protein, protolysate, somatomedin, enzyme, protease, enzyme inhibitor, protease inhibitor, coenzyme, peptide for example two-, three-, four-, five-and six peptides, carbohydrate is for example single-, two-, three-and oligosaccharide, polysaccharide, glycosaminoglycans, glycosaminoglycans subunit (glycosaminoglycan subunits), purine, pyrimidine, nucleotide, nucleoside, carboxylic acid, saturated and unsaturated fatty acid, lipid, sphingol, sphingolipid, glycosyl sphingolipid, thioester, phospholipid, sterol, plant sterol, saponin, flavone compound, phenol, polyphenol, terpene, alkaloid, benzofuran, trace element and salt thereof, polyhydric alcohol, the antimicrobial composition, antimicrobial peptide, the UV absorbent, vitamin, provitamin, retinoid, carotenoid, chelating agen, wetting agent, the epidermal barrier function regulator, skin recovers and the regeneration composition, tight and the anti-wrinkle agent of skin, alleviate and antiinflammatory, the antipruritic composition, the anti-dandruff composition, the decortication composition is α or β hydroxy carboxylic acid for example, antioxidant, free radical scavenger, the UV-quencher, sebum is regulated and anti-acne agent, tractive trace regulator, the skin immune system regulator, skin lightener, the skin tanning agent, anti--the loss of weight agent, the skin microcirculation regulator, the principal character of rosacea is the regulator of flushing and astable erythema for example, little blood streak and telangiectasis regulator, antifungal and composition thereof.
10. according to the cosmetic composition of claim 9, it is characterized in that described additional skin nursing composition is selected from Melatonin, carbamide, kreatinin, dimethylethanolamine, serine, glycine, aspartic acid, cysteine, glutamine, lysine, arginine, Aspartic Acid, glutamic acid, N-acetylcystein, citrulline, collagen, gelatin, albumin, casein, elastin laminin, keratin, sericin, fibroin, the anti-keratin microfilament is assembled albumen, transforming growth factor, insulin like growth factor, epidermal growth factor, acidity and basic fibroblast growth factor, nerve growth factor, keratinocyte growth factor, hepatocyte growth factor, derived from hematoblastic somatomedin, granulocyte-macrophage colony-stimulating factor, vascular endothelial cell growth factor, papain, bromelain, subtilisin, superoxide dismutase, lactoperoxidase, phospholipase, T-5398, tranexamic acid, soybean trypsin inhibitor, Bao Man-Bi Erke inhibitor, LEKTI, aprotinin, elastin, SLPI, alpha1-antitrypsin, α 1-chymotrypsin inhibitor, cholesterol sulfate, leupeptin, chymostatin, tissue inhibitor of metalloproteinase;
Figure FPA00001178290600031
Series compound; the mustard extract; coenzyme Q10; nicotiamide; nicotinamide adenine dinucleotide; nicotinamide-adenine dinucleotide phosphate; coenzyme A; actimide; flavin adenine dinucleotide (FAD); flavin mononucleotide (FMN); carnosine; H-β Ala-Pro-Dab-NH benzyl; Cu (II)-H-Gly-His-Lys-OH; H-Gly-Leu-Phe-OH; anti-9 vaccenic acids-Lys-Phe-Lys-OH; palmityl-Lys-Val-Lys-OH; H-Lys-Pro-Val-OH; palmityl-Lys-Val-Dab-OH; H-Arg-Ser-Arg-Lys-OH, palmityl-Lys-Val-Dab-Thr-OH; H-Gly-Pro-Arg-Pro-Ala-NH2; palmityl-Lys-Thr-Thr-Lys-Ser-OH; acetyl group-Glu-Glu-Met-Gln-Arg-ArgNH 2Glucose; fructose; mannose; dihydroxyacetone; Erythrulose; sucrose; trehalose; maltose; galactomannan; glucomannan; beta glucan; carrageenin; glycogen; chitosan; lentinan; lichenin; inulin; fucose; alginate; xyloglucan; glucosan; amylose; levan; xanthan gum; amylopectin; hyaluronan; chondroitin sulfate; heparin; dermatan sulfate; glucuronic acid; N-acetyl-glucosamine; allantoin; uric acid; adenosine; adenosine monophosphate; adenosine 5 '-triphosphate; kinetins; lactic acid; citric acid; glycolic; Azelaic Acid; salicylic acid; thioctic acid; the 2-pyrrolidone-5-carboxylic acid; urocanic acid; caffeic acid; linoleic acid; oleic acid; Palmic acid; conjugated linoleic acid; squalane; Squalene; monoglyceride; diglyceride; triglyceride; vaseline; lanoline; phytosphingosine; ceramide; glycoeeramide; cerebroside; ganglioside; sulfatide; phosphatidylcholine; Phosphatidylserine; PHOSPHATIDYL ETHANOLAMINE; cholesterol; sitosterol; stigmasterol; brassicasterol; lupeol; glycyrrhizin; rutin; Quercetin; genistein; daidzein; fisetin; myricetin; luteolin; hesperetin; silibinin; silymarin; the celery flavin; epigallocatechin; epigallocatechin gallate; resveratrol; nordihydroguaiaretic acid; the ellagic acid resorcinol; enoxolone; farnesol; α-bisabolol; β-bisabolol; caffeine; theophylline; theobromine; usnic acid; zinc-; selenium-; manganese-salt; glycerol; propylene glycol; butanediol; sorbitol; erithritol; hexanediol; plant triol; pyrrole sulfur zinc; sozin; the cathepsin inhibin; skin enemy rhzomorph; histatins; benzoate; anthranilate; Salicylate; cinnamate; benzophenone; Parsol TM340, benzimidazole, benzotriazole, Tinosorb TMM, triazine, Tinosorb TMS, polysiloxanes, as Parsol TMSLX, titanium dioxide, zinc oxide, melanin, vitamin A, vitamin B group, vitamin C, vitamin D, vitamin E, retinal, retinal, tretinoin, isotretinoin, alitretinoin, etretinate, acitretin, tazarotene, bexarotene, alpha-carotene, beta-carotene, lycopene, luteine, cryptoxanthin, astaxanthin, ethylenediaminetetraacetic acid, deferoxamine, sugared even acyl dioxime,
Figure FPA00001178290600041
Figure FPA00001178290600042
Yeast extract, comfrey extract, Semen Ginkgo extrac, Herba Centellae,
Figure FPA00001178290600043
Flos Chrysanthemi extract, aloe vera, Flos Inulae extract, Radix Glycyrrhizae extract, Radix Hamamelidis Mollis extract,
Figure FPA00001178290600044
Radix Oenotherae erythrosepalae oil, green tea extract,
Figure FPA00001178290600045
Prunus africana extract, Flos Carthami Thymi Serpylli Herba extract, Herba Centellae extract, arnica montana extract,
Figure FPA00001178290600046
Radix Glycyrrhizae extract,
Figure FPA00001178290600047
The Guarana extract,
Figure FPA00001178290600048
Metronidazole, ketoconazole, ciclopirox olamine, tea tree oil and derivant thereof and their mixture.
11., it is characterized in that it also comprises one or several dermatological carriers according to the cosmetic composition of one of claim 9 and 10.
12. cosmetic composition according to one of claim 9-11; it is characterized in that it comprises the chemical compound of formula (I); described chemical compound becomes solution, dispersion, Emulsion, microemulsion, nano-emulsion or capsule in carrier; preferably in liposome or Chylomicron, become big-, little-or Nano capsule; perhaps be encapsulated in big-, little-or nano-particle or microsponge (microsponges) in, granulating or be absorbed on powdered organic polymer, Talcum, bentonite and the associated minerals carrier.
13., it is characterized in that it can be solution, Emulsion (oil-in-water and Water-In-Oil), milk, lotion, dispersion, ointment, gel form and tacky surfaces activating agent and Emulgating polymers, brilliantine, shampoo, soap, gel, lyophilized preparation (lyophilisate), powder, bar rod, pen, spray, health oil, facial film or patch form according to the cosmetic composition of one of claim 9-11.
14. the protease method of urokinase particularly in the inhibition skin is characterized in that using and comprises one or more formulas (I) compound compositions on skin and/or scalp according to one of claim 9-13.
15., it is characterized in that described compositions comprises benzyl sulfonyl-D-Ser-Gly-(4-amidino groups-benzyl amide), benzyl sulfonyl-D-Ser-Ala-(4-amidino groups-benzyl amide), benzyl sulfonyl-D-Ser-homoPhe-(4-amidino groups-benzyl amide) or benzyl sulfonyl-D-Ser-Lys-(4-amidino groups-benzyl amide) or its salt according to the method for claim 14.
16. non-therapeutic purposes be used to maintain, repair and/or improve skin hydration with, through the epidermis loss of moist, improve skin and/or scalp barrier unusually as the beauty method of dry skin situation, pruritus, the dandruff and/or sensitive skin consciousness, it is characterized in that using and comprise one or more formulas (I) compound compositions on skin and/or scalp according to one of claim 9-13.
17., it is characterized in that described compositions comprises benzyl sulfonyl-D-Ser-Gly-(4-amidino groups-benzyl amide), benzyl sulfonyl-D-Ser-Ala-(4-amidino groups-benzyl amide), benzyl sulfonyl-D-Ser-homoPhe-(4-amidino groups-benzyl amide) or benzyl sulfonyl-D-Ser-Lys-(4-amidino groups-benzyl amide) or its salt according to the method for claim 16.
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